Abstract - Technology Core This U19 proposes a novel and fully integrated approach to understanding disease progression and treatment response in tuberculosis (TB). We will combine traditional approaches to understanding the pathophysiology of TB, bacterial genetics and immunology, with systems biology approaches including genomics, transcriptomics, metabolomics, lipidomics, proteomics, and computational modeling. We will apply HTP ?Omics? technologies and systems analysis to murine and mycobacterial studies and to human field studies in tuberculosis. Data generated by HTP and targeted state-of-the-art approaches will be integrated through bioinformatic and modeling approaches, which, combined with domain expertise, will lead to a deep understanding of the molecular networks that underlie the progression of TB infection and response to treatment, and predict complex biological behaviors that lead to either containment or active disease; treatment cure or relapse. Multiple innovative HTP technologies will be leveraged and enhanced through this program. These technologies have been established in multiple experimental systems and will be customized and further developed for their application to this program and to clinical samples as appropriate. These developments will ensure data quality, and maximize the efficiency of data generation. The approaches chosen are innovative and state-of-the-art and will maximize our ability to complement and extend the existing comprehensive network models and provide spatial perspective for models generated as part of the original OTB program. We will disseminate modifications and improvements to extant technologies and detailed protocols broadly to enable adoption and further development by the community.